[DNA-binding activity of bis-netropsins containing a cis-diaminoplatinum group between two netropsin fragments].
The binding to DNA of Pt-bis-Nt and its modified analogue (Pt*-bis-Nt), which differs from Pt-bis-Nt by the fact that the connecting chain between two netropsin fragments contains two additional glycine residues, has been studied. Elongating the chain in the bis-netropsin molecule increases the cytotoxicity and leads to a complete disappearance of the antiherpetic activity of bis-netropsin. A study of the binding of two bis-netropsins with the oligonucleotide duplex containing an AT cluster, which is present at the replication initiation site of herpes virus (OriS), revealed significant structural differences between complexes of bis-netropsins with this DNA oligomer. It was shown by CD spectroscopy that the binding of Pt-bis-Nt in the elongated conformation and in the form of a hair-pin with the parallel orientation of two bis-netropsin fragments makes a greater contribution than it is the case in the complex formation with Pt*-bis-Nt. At high binding rates, Pt*-bis-Nt binds to the AT cluster in OriS predominantly in the form of associates based on the antiparallel double-stranded pyrrolcarboxyamide motif. The interaction of Pt-bis-Nt and Pt*-bis-Nt with the single-stranded oligonucleotide (64 nt), which corresponds to the upper strand at the replication initiation site of herpes virus (OriS*), was also studied. Substantial differences in the binding of bis-netropsins with OriS* and thermostability of the resulting complexes were found by CD spectroscopy and by studying the melting of complexes of bis-netropsins with OriS*.
Surovaia
A N
AN
Grokhovskiĭ
S L
SL
Bazhulina
N P
NP
Gurskiĭ
G v
Gv
D000998:Antiviral Agents / Q000737:chemistry*; D004279:DNA, Viral / Q000737:chemistry*; D006564:Herpesviridae / Q000737:chemistry*; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry*; D018741:Replication Origin
D000998:Antiviral Agents; D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D009944:Organoplatinum Compounds; D009429:Netropsin; C032161:bis-netropsin